SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response

SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant ( SF3B1 MUT ) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARP...

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Published in:	Nature genetics Vol. 55; no. 8; pp. 1311 - 1323
Main Authors:	Bland, Philip, Saville, Harry, Wai, Patty T., Curnow, Lucinda, Muirhead, Gareth, Nieminuszczy, Jadwiga, Ravindran, Nivedita, John, Marie Beatrix, Hedayat, Somaieh, Barker, Holly E., Wright, James, Yu, Lu, Mavrommati, Ioanna, Read, Abigail, Peck, Barrie, Allen, Mark, Gazinska, Patrycja, Pemberton, Helen N., Gulati, Aditi, Nash, Sarah, Noor, Farzana, Guppy, Naomi, Roxanis, Ioannis, Pratt, Guy, Oldreive, Ceri, Stankovic, Tatjana, Barlow, Samantha, Kalirai, Helen, Coupland, Sarah E., Broderick, Ronan, Alsafadi, Samar, Houy, Alexandre, Stern, Marc-Henri, Pettit, Stephen, Choudhary, Jyoti S., Haider, Syed, Niedzwiedz, Wojciech, Lord, Christopher J., Natrajan, Rachael
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01.08.2023 Nature Publishing Group
Subjects:	13/106 13/51 13/89 631/1647/2217 631/208/212/2019 631/208/212/2166 631/67/1484 631/67/1990/283/1895 64/60 82/58 96/106 96/109 96/95 Adenosine diphosphate Agriculture Animal Genetics and Genomics Anticancer properties Antitumor activity Ataxia Biomarkers Biomedical and Life Sciences Biomedicine BRCA1 Protein - genetics Cancer Cancer Research Cell cycle Cell Line, Tumor CHK1 protein Cyclin-dependent kinase Cyclin-dependent kinase 2 Cyclin-dependent kinases DNA biosynthesis Drug screening Gene Function Genes Genomes Homologous recombination Human Genetics Humans In vivo methods and tests Intermediates Kinases Leukemia Medical prognosis Melanoma Metastases Mutation Mutation hot spots Neoplasms - drug therapy Neoplasms - genetics Phosphoproteins - genetics Poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase Inhibitors - pharmacology Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use Protein expression Proteins Replication Replication origins Ribose RNA Splicing Factors - genetics Transcription Factors - genetics Tumors
ISSN:	1061-4036, 1546-1718, 1546-1718
Online Access:	Get full text
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